Advertisement

Drug Delivery and Translational Research

, Volume 7, Issue 2, pp 228–240 | Cite as

Multi-parametric surface plasmon resonance platform for studying liposome-serum interactions and protein corona formation

  • Otto K. Kari
  • Tatu Rojalin
  • Stefano Salmaso
  • Michela Barattin
  • Hanna Jarva
  • Seppo Meri
  • Marjo Yliperttula
  • Tapani ViitalaEmail author
  • Arto Urtti
Methods Article

Abstract

When nanocarriers are administered into the blood circulation, a complex biomolecular layer known as the “protein corona” associates with their surface. Although the drivers of corona formation are not known, it is widely accepted that this layer mediates biological interactions of the nanocarrier with its surroundings. Label-free optical methods can be used to study protein corona formation without interfering with its dynamics. We demonstrate the proof-of-concept for a multi-parametric surface plasmon resonance (MP-SPR) technique in monitoring the formation of a protein corona on surface-immobilized liposomes subjected to flowing 100 % human serum. We observed the formation of formulation-dependent “hard” and “soft” coronas with distinct refractive indices, layer thicknesses, and surface mass densities. MP-SPR was also employed to determine the affinity (K D ) of a complement system molecule (C3b) with cationic liposomes with and without polyethylene glycol. Tendency to create a thick corona correlated with a higher affinity of opsonin C3b for the surface. The label-free platform provides a fast and robust preclinical tool for tuning nanocarrier surface architecture and composition to control protein corona formation.

Keywords

Multi-parametric surface plasmon resonance (MP-SPR) Protein corona Soft corona Liposome Complement system Opsonin 

Notes

Acknowledgments

We are grateful to M.Sc. Tatu Lajunen, B.Sc. Riikka Nurmi, and M.Sc. Antti Louna for the help in preparing and characterizing the control liposome formulations, and to Leena Pietilä and Dr. Mari Palviainen for the help with serum collection and pooling. Liposomes coated with a lipidated oligo-guanidyl derivative were kindly supplied by Professor Stefano Salmaso, University of Padova. Financial support by the Academy of Finland (grants: #137053, #263861, #263567), Tekes—the Finnish Funding Agency for Innovation EV-Extra-Tox project and the Professor Pool—Orion Research Foundation are gratefully acknowledged.

Compliance with ethical standards

All the reported experiments are in compliance with current Finnish law.

Conflict of interest

The authors declare that they have no conflicts of interest. T.R. is affiliated with BioNavis Ltd., Ylöjärvi, Finland.

Supplementary material

13346_2016_320_MOESM1_ESM.docx (21 kb)
ESM 1 (DOCX 20 kb)

References

  1. 1.
    Shi J, Votruba AR, Farokhzad OC, Langer R. Nanotechnology in drug delivery and tissue engineering: from discovery to applications. Nano Lett. 2010;10:3223–30.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Nyström AM, Fadeel B. Safety assessment of nanomaterials: implications for nanomedicine. J Control Release. 2012;161:403–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Bertrand N, Leroux J-C. The journey of a drug-carrier in the body: an anatomo-physiological perspective. J Control Release. 2012;161:152–63.CrossRefPubMedGoogle Scholar
  4. 4.
    Knop K, Hoogenboom R, Fischer D, Schubert US. Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew Chemie - Int Ed. 2010;49:6288–308.CrossRefGoogle Scholar
  5. 5.
    Hamad I, Al-hanbali ЌO, Hunter AC, Rutt KJ, Andresen TL, Moghimi SM. Switching of complement activation pathways at the Nanosphere serum Interface : implications for stealth nanoparticle engineering. ACS Nano. 2010;4:6629–38.CrossRefPubMedGoogle Scholar
  6. 6.
    Arima Y, Toda M, Iwata H. Complement activation on surfaces modified with ethylene glycol units. Biomaterials. 2008;29:551–60.CrossRefPubMedGoogle Scholar
  7. 7.
    Salmaso S, Caliceti P. Stealth properties to improve therapeutic efficacy of drug nanocarriers. J Drug Deliv. 2013;2013:1–19.CrossRefGoogle Scholar
  8. 8.
    Mahon E, Salvati A, Baldelli Bombelli F, Lynch I, Dawson KA. Designing the nanoparticle–biomolecule interface for “targeting and therapeutic delivery.”. J Control Release. Elsevier B.V2012;161:164–74.CrossRefPubMedGoogle Scholar
  9. 9.
    Szebeni J, Muggia F, Gabizon A, Barenholz Y. Activation of complement by therapeutic liposomes and other lipid excipient-based therapeutic products: prediction and prevention. Adv Drug Deliv Rev. Elsevier B.V2011;63:1020–30.CrossRefPubMedGoogle Scholar
  10. 10.
    Chanan-Khan A. Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil(R)): possible role in hypersensitivity reactions. Ann Oncol. 2003;14:1430–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Lynch I, Cedervall T, Lundqvist M, Cabaleiro-Lago C, Linse S, Dawson KA. The nanoparticle-protein complex as a biological entity; a complex fluids and surface science challenge for the twenty-first century. Adv Colloid Interf Sci. 2007;134-135:167–74.CrossRefGoogle Scholar
  12. 12.
    Palchetti S, Colapicchioni V, Digiacomo L, Caracciolo G, Pozzi D, Capriotti AL, et al. The protein corona of circulating PEGylated liposomes. Biochim Biophys Acta - Biomembr. Elsevier B.V2016;1858:189–96.CrossRefGoogle Scholar
  13. 13.
    Walczyk D, Bombelli FB, Monopoli MP, Lynch I. Dawson K a. What the cell “sees” in bionanoscience. J AmChem Soc. 2010;132:5761–8.CrossRefGoogle Scholar
  14. 14.
    Cedervall T, Lynch I, Lindman S, Berggård T, Thulin E, Nilsson H, et al. Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proc Natl Acad Sci U S A. 2007;104:2050–5.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Corbo C, Molinaro R, Parodi A, Furman NET, Salvatore F, Tasciotti E. The impact of nanoparticle protein corona on cytotoxicity, immunotoxicity and target drug delivery. Nanomedicine. 2016;11:81–100.CrossRefPubMedGoogle Scholar
  16. 16.
    Docter D, Westmeier D, Markiewicz M, Stolte S, Knauer SK, Stauber RH. The nanoparticle biomolecule corona: lessons learned—challenge accepted? Chem Soc Rev Royal Society of Chemistry. 2015;44:6094–121.CrossRefGoogle Scholar
  17. 17.
    Tenzer S, Docter D, Kuharev J, Musyanovych A, Fetz V, Hecht R, et al. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nat Nanotechnol. 2013;8:772–81.CrossRefPubMedGoogle Scholar
  18. 18.
    Lundqvist M, Stigler J, Elia G, Lynch I, Cedervall T, Dawson KA. Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proc Natl Acad Sci U S A. 2008;105:14265–70.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Lundqvist M. Nanoparticles: tracking protein corona over time. Nat Publ Gr. 2013;8:1–2.Google Scholar
  20. 20.
    Monopoli MP, Åberg C, Salvati A, Dawson KA, Åberg C, Salvati A, et al. Biomolecular coronas provide the biological identity of nanosized materials. Nat Nanotechnol. Nature Publishing Group2012;7:779–86.CrossRefPubMedGoogle Scholar
  21. 21.
    Carroll MV, Sim RB. Complement in health and disease. Adv Drug Deliv Rev. 2011;1–11. Elsevier B.V.Google Scholar
  22. 22.
    Pangburn MK, Schreiber RD, Müller-Eberhard HJ. C3b deposition during activation of the alternative complement pathway and the effect of deposition on the activating surface. J Immunol. 1983;131:1930–5.PubMedGoogle Scholar
  23. 23.
    Andersson J, Ekdahl KN, Lambris JD, Nilsson B. Binding of C3 fragments on top of adsorbed plasma proteins during complement activation on a model biomaterial surface. Biomaterials. 2005;26:1477–85.CrossRefPubMedGoogle Scholar
  24. 24.
    Nilsson B, Ekdahl KN, Mollnes TE, Lambris JD. The role of complement in biomaterial-induced inflammation. Mol Immunol. 2007;44:82–94.CrossRefPubMedGoogle Scholar
  25. 25.
    Arima Y, Toda M, Iwata H. Surface plasmon resonance in monitoring of complement activation on biomaterials. Adv Drug Deliv Rev. Elsevier B.V2011;63:988–99.CrossRefPubMedGoogle Scholar
  26. 26.
    Granqvist N, Yliperttula M, Välimäki S, Pulkkinen P, Tenhu H, Viitala T. Control of the morphology of lipid layers by substrate surface chemistry. Langmuir. 2014;30:2799–809.CrossRefPubMedGoogle Scholar
  27. 27.
    Kretschmann E. Determination of optical constants of metals by excitation of surface plasmons. Zeitschrift Fur Phys. 1971;241:313–24.CrossRefGoogle Scholar
  28. 28.
    Granqvist N, Liang H, Laurila T, Sadowski J, Yliperttula M, Viitala T. Characterizing ultrathin and thick organic layers by surface plasmon resonance three-wavelength and waveguide mode analysis. Langmuir. 2013;29:8561–71.CrossRefPubMedGoogle Scholar
  29. 29.
    Bakhtiar R. Surface plasmon resonance spectroscopy: a versatile technique in a biochemist ’ s toolbox. 2013.Google Scholar
  30. 30.
    Albers WM, Vikholm-lundin I. Surface plasmon resonance on nanoscale organic films. 1988;83–125.Google Scholar
  31. 31.
    Liang H, Miranto H, Granqvist N, Sadowski JW, Viitala T, Wang B, et al. Surface plasmon resonance instrument as a refractometer for liquids and ultrathin films. Sensors Actuators B Chem. Elsevier B.V2010;149:212–20.CrossRefGoogle Scholar
  32. 32.
    Abraham SA, Waterhouse DN, Mayer LD, Cullis PR, Madden TD, Bally MB. The liposomal formulation of doxorubicin. Methods Enzymol. 2005;391:71–97.CrossRefPubMedGoogle Scholar
  33. 33.
    Bersani S, Salmaso S, Mastrotto F, Ravazzolo E, Semenzato A, Caliceti P. Star-like oligo-arginyl-maltotriosyl derivatives as novel cell-penetrating enhancers for the intracellular delivery of colloidal therapeutic systems. Bioconjug Chem. 2012;23:1415–25.CrossRefPubMedGoogle Scholar
  34. 34.
    Löfås S, Johnsson B. A novel hydrogel matrix on gold surfaces in surface plasmon resonance sensors for fast and efficient covalent immobilization of ligands. J Chem Soc Chem Commun. 1990;1526.Google Scholar
  35. 35.
    Peterlinz KA, Georgiadis R. Two-color approach for determination of thickness and dielectric constant of thin films using surface plasmon resonance spectroscopy. Opt Commun North-Holland. 1996;130:260–6.CrossRefGoogle Scholar
  36. 36.
    Grassi JH, Georgiadis RM. Temperature-dependent refractive index determination from critical angle measurements: implications for quantitative SPR sensing. Am Chem Soc. 1999.Google Scholar
  37. 37.
    Zhou M, Otomo A, Yokoyama S, Mashiko S. Estimation of organic molecular film structures using surface–plasmon resonance spectroscopy. Thin Solid Films. 2001;393:114–8.CrossRefGoogle Scholar
  38. 38.
    Viitala T, Granqvist N, Hallila S, Raviña M, Yliperttula M. Elucidating the signal responses of multi-parametric surface plasmon resonance living cell sensing: a comparison between optical modeling and drug-MDCKII cell interaction measurements. PLoS One. Public Library of Science2013;8:e72192.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Granqvist N, Hanning A, Eng L, Tuppurainen J, Viitala T. Label-enhanced surface plasmon resonance: a new concept for improved performance in optical biosensor analysis. Sensors (Basel). Multidisciplinary Digital Publishing Institute (MDPI)2013;13:15348–63.CrossRefGoogle Scholar
  40. 40.
    Karlsson R, Fält A. Experimental design for kinetic analysis of protein-protein interactions with surface plasmon resonance biosensors. J Immunol Methods. 1997;200:121–33.CrossRefPubMedGoogle Scholar
  41. 41.
    Zhao H, Brown PH, Schuck P. On the distribution of protein refractive index increments. Biophys J Biophysical Society. 2011;100:2309–17.Google Scholar
  42. 42.
    Ball V, Ramsden JJ. Buffer dependence of refractive index increments of protein solutions. Biopolymers. 1998;46:489–92.CrossRefGoogle Scholar
  43. 43.
    Sadowski JW, Korhonen IKJ, Peltonen JPK. Characterization of thin films and their structures in surface plasmon resonance measurements. Opt Eng. 1995;34:2581–6.CrossRefGoogle Scholar
  44. 44.
    Kretschmann E, Raether H. Radiative decay of non-radiative surface plasmons excited by light. Z Naturforsch. 1968;23:2135–6.Google Scholar
  45. 45.
    Hall D. Kinetic models describing biomolecular interactions at surfaces. Handb Surf Plasmon Reson. 2008;81–122.Google Scholar
  46. 46.
    Hamad I, Hunter AC, Szebeni J, Moghimi SM. Poly(ethylene glycol)s generate complement activation products in human serum through increased alternative pathway turnover and a MASP-2-dependent process. Mol Immunol. 2008;46:225–32.CrossRefPubMedGoogle Scholar
  47. 47.
    Gref R, Lück M, Quellec P, Marchand M, Dellacherie E, Harnisch S, et al. “Stealth” corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surfaces B Biointerfaces. 2000;18:301–13.CrossRefPubMedGoogle Scholar
  48. 48.
    Lundquist A, Hansen SB, Nordström H, Danielson UH, Edwards K. Biotinylated lipid bilayer disks as model membranes for biosensor analyses. Anal Biochem. Elsevier Inc.2010;405:153–9.CrossRefPubMedGoogle Scholar
  49. 49.
    Nel AE, Mädler L, Velegol D, Xia T, Hoek EMV, Somasundaran P, et al. Understanding biophysicochemical interactions at the nano-bio interface. Nat Mater Nature Publishing Group. 2009;8:543–57.CrossRefGoogle Scholar

Copyright information

© Controlled Release Society 2016

Authors and Affiliations

  • Otto K. Kari
    • 1
  • Tatu Rojalin
    • 1
  • Stefano Salmaso
    • 2
  • Michela Barattin
    • 2
  • Hanna Jarva
    • 3
  • Seppo Meri
    • 3
  • Marjo Yliperttula
    • 1
    • 2
  • Tapani Viitala
    • 1
    Email author
  • Arto Urtti
    • 1
    • 4
  1. 1.Centre for Drug Research and Division of Pharmaceutical Biosciences, Faculty of PharmacyUniversity of HelsinkiHelsinkiFinland
  2. 2.Department of Pharmaceutical and Pharmacological SciencesUniversity of PadovaPadovaItaly
  3. 3.Department of Bacteriology and Immunology, Immunobiology Research Program, Faculty of Medicine, and HUSLAB, Division of Clinical MicrobiologyHelsinkiFinland
  4. 4.School of PharmacyUniversity of Eastern FinlandKuopioFinland

Personalised recommendations